Department of Orthopedics, Lanzhou University Second Hospital, Second Clinical School, Lanzhou University, Lanzhou 730030, China.
Key Laboratory of Orthopaedics of Gansu Province, Lanzhou University, Lanzhou 730030, China.
Biomolecules. 2024 Jul 3;14(7):791. doi: 10.3390/biom14070791.
The ubiquitin-proteasome system (UPS) maintains intracellular protein homeostasis and cellular function by regulating various biological processes. Ubiquitination, a common post-translational modification, plays a crucial role in the regulation of protein degradation, signal transduction, and other physiological and pathological processes, and is involved in the pathogenesis of various cancers, including osteosarcoma. Osteosarcoma, the most common primary malignant bone tumor, is characterized by high metastatic potential and poor prognosis. It is a refractory bone disease, and the main treatment modalities are surgery combined with chemotherapy. Increasing evidence suggests a close association between UPS abnormalities and the progression of osteosarcoma. Due to the complexity and pleiotropy of the ubiquitination system, each step in the ubiquitination process can be targeted by drugs. In recent years, research and development of inhibitors targeting the ubiquitin system have increased gradually, showing great potential for clinical application. This article reviews the role of the ubiquitination system in the development and treatment of osteosarcoma, as well as research progress, with the hope of improving the therapeutic effects and prognosis of osteosarcoma patients by targeting effective molecules in the ubiquitination system.
泛素-蛋白酶体系统（UPS）通过调节各种生物过程来维持细胞内蛋白质的内稳态和细胞功能。泛素化是一种常见的翻译后修饰，在蛋白质降解、信号转导和其他生理及病理过程的调控中起着关键作用，并且参与了多种癌症的发病机制，包括骨肉瘤。骨肉瘤是最常见的原发性恶性骨肿瘤，其具有高转移潜能和不良预后的特点。它是一种难治性骨疾病，主要的治疗方式是手术结合化疗。越来越多的证据表明 UPS 异常与骨肉瘤的进展密切相关。由于泛素化系统的复杂性和多效性，泛素化过程的每个步骤都可以作为药物作用的靶点。近年来，针对泛素系统的抑制剂的研究和开发逐渐增加，显示出了巨大的临床应用潜力。本文综述了泛素化系统在骨肉瘤发生和治疗中的作用及研究进展，希望通过针对泛素化系统中的有效分子，改善骨肉瘤患者的治疗效果和预后。
